Although methadone maintenance reduces illicit drug use, a significant portion of methadone maintained patients continue to abuse drugs. This involves behaviors, including intravenous needle-sharing and high-risk sexual behavior, which promote the spread of the HIV virus. We hypothesize that approximately 30% of these patients may have affective disorder and use illicit drugs in an attempt to "self-medicate". In such patients, effective treatment of the affective disorder should also decrease drug usage and its associated risk of transmission of the HIV virus. To date, controlled trials of tricyclic antidepressants in methadone maintenance patients have been inconclusive, particularly regarding drug abuse outcome. However, these studies are flawed by low dosage, short trial lengths, and reliance on cross-sectional symptoms to diagnose affective disorder. We will select methadone maintenance patients using lifetime historical criteria for depression and will randomize them in a 12-week study with a parallel design comparing imipramine and placebo. We hypothesize that the imipramine group will have less depression, less illicit drug use, less needle-sharing and less high risk sexual behavior compared to placebo treated patients. Following the 12-weeks, responders will be continued on open treatment for an additional 6 weeks and then enter a double-blind placebo-controlled 6 month discontinuation trial. This will test whether imipramine has a long-term effect in diminishing illicit drug use and high risk behavior. We will also perform an assessment of diagnosis and high risk behavior in a randomly selected sample from our two methadone maintenance clinics to assess to what proportion of patients our results may generalize. If imipramine is effective in these depressive disorders and leads to a reduction of I.V. drug use and high risk sexual behavior even in a small portion of methadone maintained patients, this would be an important step in diminishing the spread of HIV infection.